CORE A HISTOPATHOLOGY ? Summary: The Histopathology Core A provides services and mechanisms for histopathologic characterization and quality assurance of tissues from both human subjects and rodent models of gastric inflammation and neoplasia. Specifically, the Core will provide histology and immunohistochemistry services with interpretation by pathologists experienced in gastric pathology and laser capture microdissection services. Dr. Blanca Piazuelo, GI pathologist, will serve as Director of Core A, and Dr. Pelayo Correa, the former Core Director, will continue as a Co-Investigator. Dr. Barbara Schneider, a molecular biologist with ample expertise in laser capture microdissection, will serve as a Co-Investigator. Mr. Alberto Delgado, an experienced histotechnologist, will perform all histochemistry and immunohistochemistry procedures. Dr. Kay Washington, the Director of Gastrointestinal Pathology at Vanderbilt, will collaborate in the histopathologic interpretation of rodent and human gastric tissues. Drs. Douglas R. Morgan and Luis E. Bravo (Fieldwork Core C) will collaborate on providing human gastric tissues from Central American and Colombian participants for processing and histopathological interpretation by the Core. The Histopathology Core laboratory is fully equipped to perform all techniques planned in this proposal. All three of the component projects of this Program Project Grant rely heavily upon morphologic analysis of gastric tissues from human subjects and/or rodent models of Helicobacter pylori-induced disease. During the past funding period, the Histopathology Core provided services contributing to 31 peer-reviewed publications related to PPG Projects. For the next funding period, the Histopathology Core will receive de-identified paraffin-embedded gastric tissues from human subjects from Colombia and Central America in Project 1 and collected by Core C, and rodent gastric specimens from experiments in Project 3. Rodent gastric tissues will be processed and embedded in paraffin, and all human and animal tissues will be processed for H&E staining; histopathological interpretation will be provided for Projects 1, 2, and 3. Additional staining procedures for human tissues include staining of mucins (AB-PAS and HID-AB) for the classification of intestinal metaplasia, and a modified Steiner silver stain for the identification of H. pylori. In support of Project 3, the Core will perform histopathologic interpretation of tissues from gerbils infected with clinical isolates of H. pylori and also perform immunohistochemistry with scoring for spermine oxidase (SMOX), phosphorylated EGFR and ERBB2, and the pEGFR?ERBB2 dimer that Project 3 has implicated as a molecular signature of gastric carcinogenesis, along with staining for oxidative DNA damage and apoptosis. The Core will also perform laser capture microdissection as needed for methylation studies in Project 1. All data generated by the Histopathology Core A will be deposited in Administrative Core B (Director, Dr. Keith Wilson) for statistical analyses (by Dr. Robertino Mera) and unification of databases.